The effects of age and disease on the bioavailability and pharmacokinetics of drugs such as corticosteroids which are in frequent clinical use and cause a high incidence of adverse reactions will be examined. Prednisone, prednisolone, and cortisol disposition will be studied in patients with nephrotic syndrome, asthma (adult and children), and during pregnancy. The 'steroid-sparing' interaction of troleandomycin with methylprednisolone and the bioavailability of cortisol in patients with inflammatory bowel disease will be evaluated. Suitable patients will be examined pharmacokinetically in the midst of conventional drug therapy and data compared with that from normal subjects. The kinetics and mechanisms of dose-dependence of prednisolone in man will be studied including prednisone/prednisolone interconversion, nonlinear binding to plasma transcortin and albumin, biotransformation pathways, and renal clearance. Pharmacodynamic models will be sought for nonlinear prednisolone disposition and aspects of circadian-episodic secretion of cortisol. Improved high performance liquid chromatographic assays for steroids and metabolites will be evolved. Animal models such as the perfused rat kidney and the rabbit will be used to further assess mechanisms of nonlinear disposition of prednisolone, drug interactions, and pharmacokinetic factors in corticosteroid pharmacodynamics.